Mulnard 2000.

Methods	Stated purpose: to determine whether oestrogen‐only HT affects global, cognitive or functional decline in women with mild to moderate Alzheimer's disease Stratification: not mentioned No. of women screened for eligibility: 153 No. randomised: 120 (CEE 0.625 mg: 42, CEE 1.25 mg: 39, placebo: 39) No. analysed: 120 Losses to follow‐up: nil Adherence to treatment: 23 drop‐outs (7 in placebo group, 7 in CEE 0.625 mg group, 9 in CEE 1.25 mg/d). Adherence to treatment was measured and was defined as the proportion of individuals who ingested at least 80% of the study medication but was not reported in the trial publication. Analysis by intention to treat: yes No. of centres: 32 Years of recruitment: not stated Design: parallel placebo‐controlled Funding: National Institute on Aging, Wyeth Ayerst
Participants	Included Women with a diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke‐Alzheimer Disease and Related Disorders Association Criteria in mild or moderate stage (study protocol specified MMSE score of 14‐28; several exceptions were made by the project director to allow for participants with MMSE scores as low as 12); female sex; previous hysterectomy (oophorectomy not required); older than 60 years; absence of major clinical depressive disorder (as measured by score < 17 on the Hamilton Depression Rating Scale (Ham D); normal gynaecological, breast and mammography results Excluded Myocardial infarction within 1 year, history of thromboembolic disease or hypercoagulable state, hyperlipidaemia, use of excluded medications (i.e. oestrogens within 3 months; current use of antipsychotics, anticonvulsants, anticoagulants, beta‐blockers, narcotics, methyldopa, clonidine or prescription cognitive‐enhancing or antiparkinson medications, including experimental medications within 60 days before baseline. Stable doses of neuroleptics, antidepressants, anxiolytics, sedatives and hypnotics were allowed). At initiation of the protocol, individuals treated with donepezil or tacrine were excluded, but a protocol amendment after 20 months of enrolment allowed stable use (minimum of 4 weeks) of these medications before screening for the study Mean age: 75 Age range: 56‐91 Means of recruitment: not stated Baseline equality of treatment groups: no significant differences between the 3 groups in terms of baseline and demographic characteristics Country: USA
Interventions	HT arm CEE oral 0.625 mg/d CEE 1.25 mg/d Control: placebo Duration: 1 year
Outcomes	Primary outcome Progression of Alzheimer's disease (Alzheimer's Disease Co‐operative Study version of the Clinical Global Impression of Change Scale)
Notes	Power calculation: 81% to detect a 29% difference in the proportion of participants who worsened in the 2 groups (60% worse in the placebo group vs 31% worse in the oestrogen group) using a 2‐tailed (alpha) =.05 (based on data from a similar trial, with 40 participants receiving placebo and 80 receiving oestrogen) * Inclusion criteria state > 60 years, but age range at baseline was 56‐91
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated in blocks of 6
Allocation concealment (selection bias)	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up stated. Analysed by intention to treat
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States double‐blinded; used "identically appearing tablets"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	States double‐blinded; no further details
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Unclear risk	Inclusion criteria state > 60 years, but age range at baseline 56‐91